How effective is Opsynvi (Macitentan and Tadalafil)?

The U.S. Food and Drug Administration (FDA) has approved Opsynvi (Macitentan and Tadalafil) for the chronic treatment of pulmonary arterial hypertension (PAH, WHO group I) in adult patients with WHO functional class (FC) II-III. Opsynvi is a combination of the endothelin receptor antagonist (ERA) macitentan and the phosphodiesterase 5 (PDE5) inhibitor Tadalafil. The individual components of Opsynvi are indicated for the treatment of patients with pulmonary hypertension. Macitentan reduced the risk of clinical deterioration events and hospitalization, while Tadalafil improved exercise capacity.

Opsynvi's marketing approval was based on data from the Phase 3 A DUE trial, which compared the efficacy and safety of Opsynvi with macitentan or Tadalafil monotherapy in 187 patients with PAH (WHO FC II-III) who were treatment-naïve or taking stable doses of an ERA or PDE5 inhibitor for at least 3 months. Patients with a pulmonary vascular resistance (PVR) of at least 240 dyn*s/cm5 were randomly assigned to receive Opsynvi (n=108), macitentan 10 mg (n=35), or Tadalafil 40 mg (n=44) once daily.

The primary endpoint was PVR (expressed as the ratio of the geometric mean to baseline) measured 16 weeks after the start of treatment. The study results showed that compared with Macitentan (treatment effect ratio, -29% [95% CI, -39%, -18%; P < 0.0001]) and tadalafil (treatment effect ratio, -2 8% [95% CI, -36%, -20%]; P < 0.0001]), Opsynvi treatment resulted in a statistically significant greater reduction in PVR, that is, Opsynvi could significantly reduce PVR. This effect was consistent among treatment-naïve patients and those previously exposed to ERA or PDE5 inhibitors.

The most common adverse reactions of Opsynvi include edema/fluid retention, anemia, and headache/migraine. The prescribing information for Opsynvi includes a boxed warning regarding the risk of embryo-fetal toxicity.